This proposal applies recently developed bioengineering techniques for the measurement of cell mechanical properties to explore neurotransmitter modulation of cochlear function. Micropipette aspiration and cytoindentation experiments will determine the stiffness of deiters' cells which anchor outer hair cells to the basilar membrane in the mammalian cochlea. Differential interference contrast and atomic force microscopy will be used to measure the force transmission from electromotile outer hair cells to dieters' cells isolated as a complex. The effects of neurotransmitters, Acetylcholine and GABA, on DC stiffness and on the efficiency of force transmission from the outer hair cell to the deiters' cell will be studied. This stiffness modulation could contribute to the remarkable frequency selectivity of mammalian hearing as well as to protect cochlear structures from intense sound energy. The experimental results for neurotransmitter modulation of DC stiffness will be applied to improve micromechanical models for fluid vibrations in the cochlea, which attempt to explain the nonlinear response of mammalian hearing from physical principles.
